New Biological Insights and Recent Therapeutic Advances in the Management of Lung Cancer: A Clinical Investigator Think Tank
Rociletinib in EGFR-mutant, advanced NSCLC with the T790M resistance mutation
2:29 minutes.
TRANSCRIPTION:
DR CARBONE: Our experience is still somewhat early with this drug. There was a very high response rate in patients who were progressing on the EGFR TKIs with T790M. I think 67% of them achieved PRs in that setting, which is quite remarkable. DR LOVE: And looking at the waterfall plot, of course, this is now in the second-line setting. Looks like everything is going down. What about toxicity? DR CARBONE: So the adverse events were nausea, fatigue and — but the unique toxicity of this agent is its hyperglycemia, which is typically well managed with oral hypoglycemic. However, they have their own sets of toxicities, and often we find these patients have intolerance to those as well. DR LOVE: What’s known about the mechanism of how this occurs? DR CARBONE: So what I’ve heard is that it’s the result of a metabolite of the drug that has a hyperglycemic effect in potentially blocking insulin receptor or something, though I don’t think it’s completely worked out. DR LOVE: So what do we know about this agent in T790-negative tumors? DR CARBONE: There is a response rate even in T790. It does happen. The current trial is only for T790-positives. DR LOVE: So Dave, where do you see this drug going? We’ll talk about the other one. And is there thought about using it up front? DR SPIGEL: Yes. So I think we all expect any day now to see an accelerated approval for this – this agent in that restricted population, which gets back to the point about are we going to have to biopsy patients in routine settings? And I think the answer is yes, that’s how this drug will be used, unless there’s a blood-based test. So another important trial is a first-line study in both T790-positive and -negative patients versus erlotinib. That’s already started. That’s called the TIGER-1 study, with rociletinib versus erlotinib. DR LOVE: Where’s that being done? DR SPIGEL: It’s a US study. DR LOVE: Hmm. Interesting. Seems like it would have to be pretty large. DR SPIGEL: Yes, it’s a large trial. It’s an ambitious study, right? I don’t know how everyone feels, but, I mean, to actually beat erlotinib is a large task. |